This grant is intended to support Dr. Lewis' additional postdoctoral training and serve as a transition period leading towards a career as an academic research professor. Dr. Reinberg's laboratory provides an excellent research and intellectual environment, and the laboratory's expertise in transcriptional biochemistry will complete Dr. Lewis' training. Dr. Lewis' research aim is to understand the regulation of the human beta -globin promoter at the transcriptional level. His immediate goals entail a more detailed study of the beta-globin promoter. His previous work identified two human beta-thalassemia mutations as defects in a novel beta-globin downstream core promoter element. Research is now directed at obtaining a mechanistic understanding of the downstream core promoter element, including its role in beta-globin regulation and the proteins necessary for its activity. Lastly, the research will study the function of the beta-globin core promoter elements in a more physiological chromatin context. This work will make important and novel contribution to our understanding of tissue-specific regulation, core promoter, and downstream element function, and promoter activity in a chromatin context.